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71.
72.
Qingzhi Wang Fengjuan Jiao Pei Zhang Jianguo Yan Zheng Zhang Feng He Qian Zhang Zexi Lv Xiang Peng Hongwei Cai Bo Tian 《Molecular neurobiology》2018,55(5):3709-3717
The molecular mechanisms responsible for the loss of dopaminergic neurons in Parkinson’s disease (PD) remain obscure. Loss of function of E3 ubiquitin ligases is associated with mitochondria dysfunction, dysfunction of protein degradation, and α-synuclein aggregation, which are major contributors to neurodegeneration in PD. Recent research has thus focused on E3 ubiquitin ligase glycoprotein 78 (GP78); however, the role of GP78 in PD pathogenesis remains unclear. Notably, cyclin-dependent kinase 5 (CDK5) controls multiple cellular events in postmitotic neurons, and CDK5 activity has been implicated in the pathogenesis of PD. Thus, we addressed the relationship between CDK5 and GP78 in MPTP-based PD models. We found that GP78 expression is decreased in MPTP-based cellular and animal PD models, and CDK5 directly phosphorylated GP78 at Ser516, which promoted the ubiquitination and degradation of GP78. Importantly, overexpression of GP78 or interference of GP78 Ser516 phosphorylation protected neurons against MPP+-induced cell death. Thus, our research reveals that the CDK5-GP78 pathway is involved in the pathogenesis of PD and could be a novel candidate drug target for the treatment of PD. 相似文献
73.
Li J Sun L Xu C Yu F Zhou H Zhao Y Zhang J Cai J Mao C Tang L Xu Y He J 《生物化学与生物物理学报(英文版)》2012,44(4):300-306
The activation of molecular chaperone heat-shock protein 90 (Hsp90) is dependent on ATP binding and hydrolysis, which occurs in the N-terminal domains of protein. Here, we have determined three crystal structures of the N-terminal domain of human Hsp90 in native and in complex with ATP and ATP analog, providing a clear view of the catalytic mechanism of ATP hydrolysis by Hsp90. Additionally, the binding of ATP leads the N-terminal domains to be an intermediate state that could be used to partially explain why the isolated N-terminal domain of Hsp90 has very weak ATP hydrolytic activity. 相似文献
74.
Using pseudo-amino acid composition and support vector machine to predict protein structural class 总被引:4,自引:0,他引:4
As a result of genome and other sequencing projects, the gap between the number of known protein sequences and the number of known protein structural classes is widening rapidly. In order to narrow this gap, it is vitally important to develop a computational prediction method for fast and accurately determining the protein structural class. In this paper, a novel predictor is developed for predicting protein structural class. It is featured by employing a support vector machine learning system and using a different pseudo-amino acid composition (PseAA), which was introduced to, to some extent, take into account the sequence-order effects to represent protein samples. As a demonstration, the jackknife cross-validation test was performed on a working dataset that contains 204 non-homologous proteins. The predicted results are very encouraging, indicating that the current predictor featured with the PseAA may play an important complementary role to the elegant covariant discriminant predictor and other existing algorithms. 相似文献
75.
Angiogenin (Ang) is known to induce cell proliferation and inhibit apoptosis by cellular signaling pathways and by direct nuclear functions of Ang, but the mechanism of action for Ang is not yet clear. The aim of present study was to identify novel binding partner of Ang and to explore the underlying mechanism. With the use of yeast two-hybrid screening system, Ang was used as the bait to screen human fetal hepatic cDNA library for interacting proteins. Four and a half LIM domains 3 (FHL3) was identified as a novel Ang binding partner. The interaction between Ang and the full length FHL3 was further confirmed by yeast two-hybrid assay, co-immunoprecipitation and GST pull-down assays. Furthermore, FHL3 was required for Ang-mediated HeLa cell proliferation and nuclear translocation of Ang. These findings suggest that the interaction between Ang and FHL3 may provide some clues to the mechanisms of Ang-regulated cell growth and apoptosis. 相似文献
76.
Kong X Li X Cai Z Yang N Liu Y Shu J Pan L Zuo P 《Cellular and molecular neurobiology》2008,28(4):569-579
(1) Neurogenesis driven by neural stem cells (NSCs) is regulated by physiological and pathological factors. Melatonin (MT)
has profound neurotrophic and neuroprotective effects. Hence, we studied the role of MT in regulating the viability and differentiation
of NSCs derived from rat ventral midbrain. (2) NSCs were isolated from the rat ventral midbrain. The viability of NSCs was
determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-ulfophenyl)-2H-tetrazolium assay. The differentiation
of NSCs was examined by analyzing the expression of the neural markers, MT receptors, brain derived neurotropic factor (BDNF)
and glial cell line-derived neurotrophic factor (GDNF) with semi-quantitative RT-PCR, immunofluorescence cytochemistry, and
Western blot. (3) Our results showed that MT could promote the viability of NSCs. In addition, MT could significantly elevate
the mRNA and protein levels of tyroxine hydroxylase (TH), a marker of dopaminergic neurons, and decrease the expression of
the astrocytes maker glial fibrillary acidic protein (GFAP). MT also increased the production of BDNF and GDNF in the cultured
NSCs. Meanwhile, we first found that two subtypes of MT receptors, MT1 and MT2, were expressed in the ventral midbrain NSCs.
(4) These results demonstrated that MT could induce NSCs to differentiate into dopaminergic neurons and decrease astrocyte
production. These findings also suggest that MT could offer a beneficial tool in guiding directional differentiation of NSCs. 相似文献
77.
78.
Using functional domain composition and support vector machines for prediction of protein subcellular location 总被引:17,自引:0,他引:17
Proteins are generally classified into the following 12 subcellular locations: 1) chloroplast, 2) cytoplasm, 3) cytoskeleton, 4) endoplasmic reticulum, 5) extracellular, 6) Golgi apparatus, 7) lysosome, 8) mitochondria, 9) nucleus, 10) peroxisome, 11) plasma membrane, and 12) vacuole. Because the function of a protein is closely correlated with its subcellular location, with the rapid increase in new protein sequences entering into databanks, it is vitally important for both basic research and pharmaceutical industry to establish a high throughput tool for predicting protein subcellular location. In this paper, a new concept, the so-called "functional domain composition" is introduced. Based on the novel concept, the representation for a protein can be defined as a vector in a high-dimensional space, where each of the clustered functional domains derived from the protein universe serves as a vector base. With such a novel representation for a protein, the support vector machine (SVM) algorithm is introduced for predicting protein subcellular location. High success rates are obtained by the self-consistency test, jackknife test, and independent dataset test, respectively. The current approach not only can play an important complementary role to the powerful covariant discriminant algorithm based on the pseudo amino acid composition representation (Chou, K. C. (2001) Proteins Struct. Funct. Genet. 43, 246-255; Correction (2001) Proteins Struct. Funct. Genet. 44, 60), but also may greatly stimulate the development of this area. 相似文献
79.
本文综述了小RNA病毒和小DNA病毒的主要结构特征,绘制出了它们的三维结构模型,从中找出了两者间的共同点和差异,为进一步研究两种病毒提供了依据。 相似文献
80.
Zenghong Ma Wei Cai Lei Wang Chenglin Du Weiwei Luo Linyu Niu Shuqing Xue Mengxin Ren Xinzheng Zhang Jingjun Xu 《Plasmonics (Norwell, Mass.)》2016,11(6):1481-1486
Magnetic hot spots, which implies confinements and enhancements of magnetic fields, are demonstrated in graphene junctions (GJs) in the mid-infrared range. The appearance of magnetic hot spots in GJs comes from the conduction currents in the junction. In further, the extinction resonance peaks suffer blue shift, along with the increases in the magnetic fields inside junction area, when the junction width reduces. In opposite to the circumstances for electric field enhancements, neither magnetic field enhancements nor resonance frequency of GJs is perturbed by the intrinsic nonlocal electronic response of graphene. Such nonlocality immunized magnetic enhancement could be explained by the polarization dependent property of nonlocal effect. 相似文献